Prostate cancer continues to be a significant health problem, both domestically and worldwide. Numerous studies have demonstrated the efficacy and safety of transperineal prostate brachytherapy in the therapy of prostate cancer. The success of brachytherapy chiefly depends on our ability to intra-operatively tailor the radiation dose to the patient's individual anatomy. Thus the objective of this research is to design, develop, and clinically test a method for intra-operative localization of the implanted seeds in relation to the prostate, to allow for intra-operative dosimetric optimization and exit dosimetry. Brachytherapy is predominantly performed with transrectal ultrasound guidance, which provides adequate real-time visualization of soft tissue anatomy, but does not show the implanted seeds. To overcome this problem, we propose registration of ultrasound to intra-operative C-arm fluoroscopy, where the implanted seeds will be reconstructed from fluoroscopy and superimposed on ultrasound. In particular, we will: (1) Design a system and workflow that is consistent with contemporary practice of prostate brachytherapy. (2) Develop optimized mathematical algorithms for reconstruction of seed implants from C-arm fluoroscopy images, spatial registration of fluoroscopy and ultrasound imaging. (3) Integrate the algorithms with an existing commercial prostate brachytherapy system and implant optimization methods. (4) Conduct Clinical System Performance Evaluation Trial on human patients. We have established the technical feasibility of this approach in a Phase-1 SBIR research grant. We are requesting Phase-2 support to develop a clinical-grade system and evaluate its technical performance on human patients. The resulting system will withstand the scrutiny of subsequent FDA approval and enter wide-spread clinical use via commercial dispersion. [unreadable] [unreadable] [unreadable]